A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas.

IMA950 immunotherapy low-grade glioma poly-ICLC varlilumab

Journal

Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420

Informations de publication

Date de publication:
27 Sep 2023
Historique:
received: 20 02 2023
medline: 28 9 2023
pubmed: 28 9 2023
entrez: 27 9 2023
Statut: aheadofprint

Résumé

Central nervous system (CNS) WHO grade 2 low-grade glioma (LGG) patients are at high risk for recurrence and with unfavorable long-term prognosis due to the treatment resistance and malignant transformation to high-grade glioma. Considering the relatively intact systemic immunity and slow-growing nature, immunotherapy may offer an effective treatment option for LGG patients. We conducted a prospective, randomized pilot study to evaluate the safety and immunological response of the multi-peptide IMA950 vaccine with agonistic anti-CD27 antibody, varlilumab, in CNS WHO grade 2 LGG patients. Patients were randomized to receive combination therapy with IMA950+poly-ICLC and varlilumab (Arm 1) or IMA950+poly-ICLC (Arm 2) before surgery, followed by adjuvant vaccines. A total of 14 eligible patients were enrolled in the study. Four patients received pre-surgery vaccines but were excluded from post-surgery vaccines due to the high-grade diagnosis of the resected tumor. No regimen-limiting toxicity was observed. All patients demonstrated a significant increase of anti-IMA950 CD8 + T-cell response post-vaccine in the peripheral blood, but no IMA950-reactive CD8 + T-cells were detected in the resected tumor. Mass cytometry analyses revealed that adding varlilumab promoted T helper type 1 effector memory CD4 + and effector memory CD8 + T-cell differentiation in the PBMC but not in the tumor microenvironment. The combinational immunotherapy, including varlilumab, was well-tolerated and induced vaccine-reactive T-cell expansion in the peripheral blood but without a detectable response in the tumor. Further developments of strategies to overcome the blood-tumor barrier are warranted to improve the efficacy of immunotherapy for LGG patients.

Sections du résumé

BACKGROUND BACKGROUND
Central nervous system (CNS) WHO grade 2 low-grade glioma (LGG) patients are at high risk for recurrence and with unfavorable long-term prognosis due to the treatment resistance and malignant transformation to high-grade glioma. Considering the relatively intact systemic immunity and slow-growing nature, immunotherapy may offer an effective treatment option for LGG patients.
METHODS METHODS
We conducted a prospective, randomized pilot study to evaluate the safety and immunological response of the multi-peptide IMA950 vaccine with agonistic anti-CD27 antibody, varlilumab, in CNS WHO grade 2 LGG patients. Patients were randomized to receive combination therapy with IMA950+poly-ICLC and varlilumab (Arm 1) or IMA950+poly-ICLC (Arm 2) before surgery, followed by adjuvant vaccines.
RESULTS RESULTS
A total of 14 eligible patients were enrolled in the study. Four patients received pre-surgery vaccines but were excluded from post-surgery vaccines due to the high-grade diagnosis of the resected tumor. No regimen-limiting toxicity was observed. All patients demonstrated a significant increase of anti-IMA950 CD8 + T-cell response post-vaccine in the peripheral blood, but no IMA950-reactive CD8 + T-cells were detected in the resected tumor. Mass cytometry analyses revealed that adding varlilumab promoted T helper type 1 effector memory CD4 + and effector memory CD8 + T-cell differentiation in the PBMC but not in the tumor microenvironment.
CONCLUSION CONCLUSIONS
The combinational immunotherapy, including varlilumab, was well-tolerated and induced vaccine-reactive T-cell expansion in the peripheral blood but without a detectable response in the tumor. Further developments of strategies to overcome the blood-tumor barrier are warranted to improve the efficacy of immunotherapy for LGG patients.

Identifiants

DOI: 10.1093/neuonc/noad185 PMID: 37758193
pubmed: 37758193
pii: 7284052
doi: 10.1093/neuonc/noad185
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Auteurs

Atsuro Saijo (A)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Department of Internal Medicine, Tokushima Prefecture Naruto Hospital, Tokushima, Japan.
ORCID: 0000-0002-7710-5498

Hirokazu Ogino (H)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Department of Respiratory Medicine & Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Nicholas A Butowski (NA)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Meghan R Tedesco (MR)

Department of Neurology, University of California, San Francisco, San Francisco, California, USA.

David Gibson (D)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.

Payal B Watchmaker (PB)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.

Kaori Okada (K)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.

Albert S Wang (AS)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Department of Pathology, University of California, San Francisco, San Francisco, California, USA.

Anny Shai (A)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Department of Pathology, University of California, San Francisco, San Francisco, California, USA.

Andres M Salazar (AM)

Oncovir Inc., Washington, DC, USA.

Annette M Molinaro (AM)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Jane E Rabbitt (JE)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.

Maryam Shahin (M)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.

Arie Perry (A)

Department of Pathology, University of California, San Francisco, San Francisco, California, USA.

Jennifer L Clarke (JL)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0002-8054-7342

Jennie W Taylor (JW)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0003-3980-5626

Mariza Daras (M)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.

Nancy Ann Oberheim Bush (NA)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Shawn L Hervey-Jumper (SL)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Joanna J Phillips (JJ)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Department of Pathology, University of California, San Francisco, San Francisco, California, USA.

Susan M Chang (SM)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Norbert Hilf (N)

Immatics Biotechnologies GmbH, Tuebingen, Germany.

Andrea Mayer-Mokler (A)

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Immatics Biotechnologies GmbH, Tuebingen, Germany.

Tibor Keler (T)

Celldex Theraepeutics, Inc., Hampton, NJ, USA.

Mitchel S Berger (MS)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Hideho Okada (H)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
ORCID: 0000-0003-0076-9920

Classifications MeSH